Literature support Test chart for the use of ImmunoCAP® Allergen components Suspicion of peanut allergy Risk for severe reactions?

Suspicion of peanut allergy Is it allergy? Risk for severe reactions? Test with ImmunoCAP® Allergen Peanut (f13) + Ara h 2 (f423) Peanut: neg Ara h 2: neg Peanut: pos Ara h 2: neg Peanut: pos Ara h 2: pos Low risk for severe reactions to peanut Risk for severe reactions to peanut High risk for severe reactions to peanut Recommendations for further testing: In geographical areas where birch is common, test for: Ara h 8 Recommendations for further testing: Risk grading: Ara h 1 (f422)  Ara h 3 (f424)  Ara h 9 (f427)  Ara h 8 (f352)  CCD (Ro214) 

Suspicion of peanut allergy Is it allergy? Risk for severe reactions?    Ara h 2 – ImmunoCAP® f423 rAra h 2 Often associated with systemic and severe reactions. Associated with cross-reactivity to tree nuts, e.g. almond and brazil nut. A peanut storage protein. Ara h 1 – ImmunoCAP® f422 rAra h 1 Often associated with clinical reactions. Associated with cross-reactivity to nuts and legume seeds, e.g. lentil and pea. Ara h 3 – ImmunoCAP® f424 rAra h 3 Associated with cross-reactivity to lupin and soybean. Ara h 9 – ImmunoCAP® f427 rAra h 9 Often associated with systemic and more severe reactions in addition to Oral Allergy Syndrome (OAS). In peanut however, severe reactions to LTP are not well documented. Stable to heat and digestion, risk for reactions also to cooked food. A LTP (Lipid Transfer Protein). Ara h 8 – ImmunoCAP® f352 rAra h 8 Often associated with local reactions such as OAS. A marker for birch-pollen related cross-reactions to peanut. A heat labile protein, cooked food is often tolerated. A PR-10 protein. CCD – ImmunoCAP® Ro214 MUXF3 Rarely associated with clinical reactions. A marker for sensitization to cross-reactive carbohydrate determinants (CCD). Present in all plants.         References: Astier C et al. J Allergy Clin Immunol 2006;118:250, Flinterman AE et al. Clin Exp Allergy 2007;37:1221, Koppelman S.J et al. Clin Exp Allergy 2004;34:583, McDermott RA et al. Clin Exp Allergy 2007;37:752, Mittag D et al. J Allergy Clin Immunol 2004;114:1410, Peeters KA et al. Clin Exp Allergy 2007;37:108

References Astier C et al. Predictive value of skin prick tests using recombinant allergens for diagnosis of peanut allergy. J Allergy Clin Immunol 2006;118(1):250-6 Flinterman AE et al. Children with peanut allergy recognize predominantly Ara h 2 and Ara h 6, which remains stable over time. Clin Exp Allergy 2007;37(8):1221-8 Koppelman SJ et al. Relevance of Ara h 1, Ara h 2 and Ara h 3 in peanut-allergic patients, as determined by immunoglobulin E Western blotting, basophil-histamine release and intracutaneous testing: Ara h 2 is the most important peanut allergen. Clin Exp Allergy 2004;34(4):583-90 McDermott RA et al. Contribution of Ara h 2 to peanut-specific, immunoglobulin E-mediated, cell activation. Clin Exp Allergy 2007;37(5):752-63 Mittag D et al. Ara h 8, a Bet v 1-homologous allergen from peanut, is a major allergen in patients with combined birch pollen and ´peanut allergy. J Allergy Clin Immunol 2004;114:1410-7 Peeters KA et al. Does skin prick test reactivity to purified allergens correlate with clinical severity of peanut allergy? Clin Exp Allergy 2007;37(1):108-15

Astier C et al. Predictive value of skin prick tests using recombinant allergens for diagnosis of peanut allergy J Allergy Clin Immunol 2006:118; 250-6 30 French patients (age 3-20 yrs) with peanut allergy reacted with specific IgE antibodies to recombinant allergens from peanut: Ara h 2: 100% Ara h 1: 50% Ara h 3: 20% Ara h 2 - the most interesting candidate for use in the diagnosis of peanut allergy Sensitization to Ara h 1 and/or Ara h 3, in addition to Ara h 2 was associated with severe reactions

Most intense/profound IgE binding Highest SPT reactivity Flinterman AE et al. Children with peanut allergy recognize predominantly Ara h 2 and Ara h 6, which remains stable over time Clin Exp Allergy 2007:37; 1221-1228 In 22 Dutch children (age 3-15 yrs), Ara h 2 and Ara h 6 were the most frequently recognized major peanut allergen components: Ara h 2: 100% Ara h 6: 80-85% Ara h 3: 50-55% Ara h 1: 45-50% Ara h 2 and Ara h 6 showed: Most intense/profound IgE binding Highest SPT reactivity

All 4 allergens were indicative of severe reactions: Peeters KA et al. Does skin prick test reactivity to purified allergens correlate with clinical severity of peanut allergy? Clin Exp Allergy 2007:37; 108-15 The majority of adult Dutch patients (n=30, age 16-70 yrs) were sensitized to Ara h 2 and Ara h 6: Ara h 2: 83%, Ara h 6: 87%, Ara h 3: 50%, Ara h 1: 53% Ara h 2 and Ara h 6 showed a higher allergenic potency than Ara h 1 and Ara h 3: More intense/profound IgE binding and higher SPT reactivity All 4 allergens were indicative of severe reactions: Both SPT reactivity to low conc of Ara h 2 and Ara h 6, and high conc of Ara h 1 and Ara h 3, were indicative of severe symptoms